Gates Foundation awards $287 million for HIV vaccine research

By TOM PAULSON, P-I REPORTER

Published
10:00 pm PDT, Tuesday, July 18, 2006

Science "as usual" has become something of an obstacle in the search for an AIDS vaccine, so the Bill & Melinda Gates Foundation today announced it is awarding $287 million to 16 research teams -- four of them in Seattle -- that have agreed to collectively veer off the beaten path.

"These grants bring together some of the best minds from around the world, more than 165 investigators from 19 countries," said Dr. Nick Hellman, interim director for the HIV/AIDS program at the Gates Foundation.

It is the largest single donation for an AIDS project by the Gateses so far and comes shortly after Melinda Gates, at last month's event announcing Warren Buffett's donation of his own billions to the Seattle philanthropy, said that her "fondest dream" is for the Gates Foundation to help find an effective HIV vaccine.

Many of the Gates grant recipients are some of the most established names in the HIV vaccine research establishment -- and, as such, responsible for business as usual. But it is what they are planning to do now and how they plan to do it that is intended to blast through the business-as-usual logjam that nearly everyone agreed has been hampering progress.

To begin with, the participating scientists all have to collaborate fully -- sharing raw data and even experimental materials -- rather than continue to compete as independent labs.

"Scientists, like artists, prefer to go their own way and do their own thing," said Dr. David Ho, one of the world's top AIDS researchers and director of the Aaron Diamond AIDS Research Center in New York City.

Ho, a maverick researcher who championed the anti-HIV medications known as protease inhibitors credited with preventing the deaths of millions with AIDS, received a $24.7 million Gates grant to investigate the critical but still incompletely understood role of fundamental immune system cells known as "dendritic cells."

"This is the kind of high-risk research that others, like NIH (National Institutes of Health), won't fund," Ho said.

Other examples of high-wire AIDS vaccine science getting Gates support: British researchers received $25.3 million to study some uniquely weird antibodies made by llamas; Swiss scientists got $15.3 million to test an altered poxvirus as an AIDS vaccine, and a Seattle team was given $19.4 million to create computer-designed synthetic proteins that will be tailor-made to thwart HIV's deadly ability to evade immune system detection.

"I'm kind of new to this whole vaccine thing," acknowledged a wild-haired David Baker, a University of Washington biochemist and wunderkind who rapidly has gained international renown for his innovative work in computerized protein analysis.

"Using computers, one can design proteins to elicit reactive antibodies," said Dr. Leo Stamatatos, an HIV/AIDS expert at Seattle Biomedical Research Institute and lead investigator on the Gates grant. Stamatatos recruited Baker and his UW colleagues to assist with the ambitious project because of their expertise at handling gargantuan analytical tasks.

Baker is the creator of a "distributed computing" network known as Rosetta@home (modeled after the extraterrestrial-seeking SETI@home) which recruits volunteers around the world to allow their home computers to be harnessed for crunching the massive amount of data needed to analyze and predict protein shapes and behavior.

"One of the single biggest limiting factors (in the field of protein analysis) has been the lack of adequate computing power," he said.

Similarly, Stamatatos said, one of the biggest problems preventing researchers from identifying proteins that potentially could provoke an antibody response to HIV has been this inability to rapidly examine and test the many different kinds of proteins involved.

"With this grant, we're going to be able to test more than 200," he said.

There are two basic arms to the immune system. One is the antibody, or humoral, response; the other is known as the cellular response. Because of HIV's ability to rapidly change its genetics and disguise its foreign nature from the immune system, nobody in the past two decades of AIDS vaccine research has been able to figure out how to provoke a meaningful antibody response to HIV.

Further, this failure led nearly all scientists to play it safe and focus only on trying to create AIDS vaccines that can elicit a cellular response, Stamatatos said, even though everyone agrees an antibody response is likely going to be needed as well.

Remember the joke about the drunk who looks for his lost keys under the streetlight, rather than back in the dark alley where he dropped them, because the light is better?

A primary goal of the $287 million in Gates grants is to encourage AIDS vaccine researchers to go back into the dark alleys and even into some new previously dark corners.

Of the 16 Gates grants, five go to research teams like the one led by Stamatatos searching for these elusive "neutralizing antibodies" while six grants go to scientific consortia focused on novel attempts at making progress with an AIDS vaccine that stimulates a cellular response.